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Peripheral Nerve Stimulation for Shoulder Pain: Dose Response

Sponsor
MetroHealth Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02928055
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), Case Western Reserve University (Other)
23
Enrollment
1
Location
3
Arms
36.9
Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this RCT is explore the mechanism for Hemiplegic Shoulder Pain (HSP) reduction due to treatment with peripheral nerve stimulation. We will explore the association of subject-specific clinical and demographic information and pain relief from PNS. We will explore the possible role of central sensitization mechanisms in perpetuating pain via measures of sensory and pain perception. Lastly, we will explore the dose-response association of muscle-contraction from PNS and pain reduction, completion of activities of daily living (ADLs), and improvement in quality of life.

Condition or Disease Intervention/Treatment Phase
  • Device: Peripheral Nerve Stimulation
 N/A

Detailed Description

Hemiplegic shoulder pain (HSP) affects up to 60% of moderate to severely impaired stroke survivors. HSP is associated with poor rehabilitation outcomes, including interference with activities of daily living (ADLs) and poor quality of life (QoL). While many treatments for HSP have been proposed, most do not result in long-term relief of pain.

The investigators developed the use of intramuscular peripheral nerve stimulation (PNS) for the treatment of HSP, which involves the temporary placement of a percutaneous intramuscular electrode to stimulate the axillary nerve motor points to the deltoid muscle. The deltoid muscle is stimulated for 6 hours per day for 3 weeks, causing comfortable, non-fatiguing contractions. This treatment, which occurs in the community setting, results in pain relief for up to 12 months when compared to treatment with a hemisling. A systematic review of randomized controlled trials (RCT) with pain as the primary outcome concluded that intramuscular PNS was the only treatment to provide long-term relief of pain for those with HSP. We have completed two RCTs that have demonstrated that a short-term PNS treatment (i.e., 3 or 6 weeks) provides pain relief. The first trial demonstrated efficacy in long-term pain relief in more than 60% of subjects for greater than 12 months. The second trial corroborated the finding that more than 60% of subjects receiving PNS achieved long-term pain reduction, and also showed that PNS reduces pain more than that achieved with physical therapy. The mechanism of action of PNS in reduction of HSP is not yet known. Thus, the primary objective of this RCT is explore the mechanism for HSP reduction.

The mechanisms behind PNS for the treatment of HSP are not known. First, individual variation may contribute to response to PNS, thus we will explore the association of subject-specific clinical and demographic information and pain relief from PNS. Secondly, our team and others have found that in the chronic stage central sensitization mechanisms may also have a role in perpetuating pain, as it does in other forms of chronic shoulder pain. These mechanisms will be explored via measures of sensory and pain perception. Finally, our approach to delivering PNS for HSP is different from other treatments in which PNS is delivered through skin surface electrodes (e.g., transcutaneous electrical nerve stimulation or TENS) in that our treatment produces repeated muscle contraction over the course of weeks. Treatments such as TENS generates tingling sensations (paresthesias) over the painful area, and pain relief following stimulation is short-lived, seldom lasting more than a few hours. We postulate that long-term pain relief for HSP after PNS treatment is due to the repeated muscle contraction that occurs daily over the course of treatment, thus we will explore the dose-response association of muscle-contraction from PNS and pain reduction, completion of activities of daily living (ADLs), and improvement in quality of life.

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Implanted PNS for Shoulder Pain in Stroke
Study Start Date :
Oct 1, 2016
Actual Primary Completion Date :
Aug 1, 2019
Actual Study Completion Date :
Oct 30, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: PNS (3 hr/day)

The PNS (3 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (3 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period.

Device: Peripheral Nerve Stimulation
The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad has an embedded power source but also serves as the anode. The 1-channel stimulator outputs a biphasic current waveform with current pulse parameter ranges suitable for PNS. The percutaneous lead is inserted using an introducer (like a hypodermic needle) which is withdrawn and the lead is retained in the muscle by a barb at its tip. After a 1-week stabilization period, stimulation is initiated (daily dose is Group-dependent). Stimulus parameters may be adjusted by the research staff as deemed appropriate. The treatment period is 3 weeks after which the lead will be removed. Total time of electrode implantation is no more than 29 days.
Other Names:
  • Intramuscular Peripheral Nerve Stimulation
  • Intramuscular Electrical Nerve Stimulation
  • Smartpatch System

    		•
    Experimental: PNS (6 hr/day)

    The PNS (6 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period.

    Device: Peripheral Nerve Stimulation
    The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad has an embedded power source but also serves as the anode. The 1-channel stimulator outputs a biphasic current waveform with current pulse parameter ranges suitable for PNS. The percutaneous lead is inserted using an introducer (like a hypodermic needle) which is withdrawn and the lead is retained in the muscle by a barb at its tip. After a 1-week stabilization period, stimulation is initiated (daily dose is Group-dependent). Stimulus parameters may be adjusted by the research staff as deemed appropriate. The treatment period is 3 weeks after which the lead will be removed. Total time of electrode implantation is no more than 29 days.
    Other Names:
  • Intramuscular Peripheral Nerve Stimulation
  • Intramuscular Electrical Nerve Stimulation
  • Smartpatch System

    		•
    Experimental: PNS (9 hr/day)

    The PNS (9 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (9 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period.

    Device: Peripheral Nerve Stimulation
    The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad has an embedded power source but also serves as the anode. The 1-channel stimulator outputs a biphasic current waveform with current pulse parameter ranges suitable for PNS. The percutaneous lead is inserted using an introducer (like a hypodermic needle) which is withdrawn and the lead is retained in the muscle by a barb at its tip. After a 1-week stabilization period, stimulation is initiated (daily dose is Group-dependent). Stimulus parameters may be adjusted by the research staff as deemed appropriate. The treatment period is 3 weeks after which the lead will be removed. Total time of electrode implantation is no more than 29 days.
    Other Names:
  • Intramuscular Peripheral Nerve Stimulation
  • Intramuscular Electrical Nerve Stimulation
  • Smartpatch System

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) [End of Treatment (EOT), EOT + 3 mo]

      Brief Pain Inventory(BPI) Short Form 3: The BPI has excellent psychometrics and is recommended for the assessment of pain in clinical trials. The developers of the BPI recommend BPI SF-3, the "pain worst" rating, as the primary response metric. The question asks participants to rate their worst pain in the prior 7-d on a 0 to 10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.

    Other Outcome Measures

    1. Adverse Events (Related) [Electrode Implant, Start of Stimulation, 1 week after start of stimulation, 2 weeks after start of stimulation, end of treatment (EOT), EOT + 1mo, EOT + 2 mo, EOT + 3 mo]

      Related adverse events are documented as Safety data.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 89 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • shoulder pain localized to the glenohumeral joint, subacromial area or deltoid insertion associated with: a) rest; b) passive abduction or external rotation range of motion (ROM); c) active abduction ROM; or, d) manual palpation;

    • shoulder pain onset or worsening after the most recent stroke;

    • weakness of shoulder abductors (≤4/5 on MRC if isolated movement is present);

    • ≥ 21-yrs old; < 90-yrs old;

    • time of stroke ≥ 3-mo;

    • duration of HSP ≥3-mo;

    • HSP with moderate to severe pain (BPI SF-3 ≥ 4);

    • cognitive and communication ability to fulfill study requirements (cognitive ability based upon a score of ≥24 on the Mini Mental Status Exam (MMSE));

    • availability of reliable adult who can assist with study procedures if necessary;

    • willing and able to report shoulder pain and other conditions and complete study visits throughout the 4 month study period.

    Exclusion Criteria:

    • joint or overlying skin infection or history of recurrent skin infections;

    • insensate skin;

    • need to take > 1 opioid and > 1 nonopioid analgesic medication for HSP;

    • regular intake of pain medications for another chronic pain;

    • botox injection or subacromial steroid injections to the shoulder within the past 12 wks;

    • receiving OT or PT for HSP;

    • bleeding disorder or INR > 3.0;

    • sensitivity to skin surface electrodes and/or medical-grade adhesives, gels, tapes;

    • medical instability;

    • pregnancy;

    • uncontrolled seizures (>1/mo for 6-mo);

    • history of cardiac arrhythmia with hemodynamic instability;

    • history of lidocaine allergy;

    • history of Parkinson's disease, SCI, TBI, MS, or ipsilateral UE lower motor neuron lesion;

    • history of complex regional pain syndrome, myofacial pain syndrome, other pain conditions (investigator discretion);

    • cardiac pacemaker or other implanted electronic device;

    • history of valvular heart disease (artificial valves, requiring antibiotics for procedures, etc.);

    • severely impaired communication.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MetroHealth Medical Center Cleveland Ohio United States 44109

    Sponsors and Collaborators

    • MetroHealth Medical Center
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    • Case Western Reserve University

    Investigators

    • Principal Investigator: Richard D Wilson, MD, MetroHealth Medical Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Richard Wilson, MD, Assistant Professor, Physical Medicine and Rehabilitation, MetroHealth Medical Center
    ClinicalTrials.gov Identifier:
    NCT02928055
    Other Study ID Numbers:
    • IRB16-00510
    • R01HD075542
    First Posted:
    Oct 7, 2016
    Last Update Posted:
    Jun 18, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by Richard Wilson, MD, Assistant Professor, Physical Medicine and Rehabilitation, MetroHealth Medical Center
    Stroke
    Shoulder Pain
    Electrical stimulation
    Neuromuscular stimulation
    Intramuscular stimulation
    Additional relevant MeSH terms:
    Shoulder Pain
    Stroke

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day)
    Arm/Group Description The PNS (3 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (3 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (6 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (9 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (9 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period.
    Period Title: Overall Study
    STARTED 8 8 7
    End of Treatment 8 8 6
    1 Month Follow up 7 7 6
    2 Month Follow up 6 7 5
    3 Month Follow up 5 6 5
    COMPLETED 5 6 5
    NOT COMPLETED 3 2 2

    Baseline Characteristics

    Arm/Group Title PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day) Total
    Arm/Group Description The PNS (3 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (3 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (6 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (9 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (9 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. Total of all reporting groups
    Overall Participants 8 8 7 23
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    100%
    7
    87.5%
    4
    57.1%
    19
    82.6%
    >=65 years
    0
    0%
    1
    12.5%
    3
    42.9%
    4
    17.4%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.75
    (6.25)
    57.5
    (8.64)
    62.86
    (5.64)
    58.52
    (7.35)
    Sex: Female, Male (Count of Participants)
    Female
    5
    62.5%
    4
    50%
    3
    42.9%
    12
    52.2%
    Male
    3
    37.5%
    4
    50%
    4
    57.1%
    11
    47.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    14.3%
    1
    4.3%
    Not Hispanic or Latino
    8
    100%
    8
    100%
    6
    85.7%
    22
    95.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    1
    12.5%
    0
    0%
    0
    0%
    1
    4.3%
    Black or African American
    4
    50%
    4
    50%
    2
    28.6%
    10
    43.5%
    White
    3
    37.5%
    4
    50%
    5
    71.4%
    12
    52.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    8
    100%
    8
    100%
    7
    100%
    23
    100%

    Outcome Measures

    1. Primary Outcome
    Title Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3)
    Description Brief Pain Inventory(BPI) Short Form 3: The BPI has excellent psychometrics and is recommended for the assessment of pain in clinical trials. The developers of the BPI recommend BPI SF-3, the "pain worst" rating, as the primary response metric. The question asks participants to rate their worst pain in the prior 7-d on a 0 to 10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.
    Time Frame End of Treatment (EOT), EOT + 3 mo

    Outcome Measure Data

    Analysis Population Description
    numbers analyzed differ at 3 month follow up due to study drop out of some subjects at 3 month follow up
    Arm/Group Title PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day)
    Arm/Group Description The PNS (3 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (3 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (6 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (9 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (9 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period.
    Measure Participants 8 8 7
    End of Treatment Score
    5.6
    6
    5.67
    3 month follow up score
    6.5
    5.2
    4.4
    2. Other Pre-specified Outcome
    Title Adverse Events (Related)
    Description Related adverse events are documented as Safety data.
    Time Frame Electrode Implant, Start of Stimulation, 1 week after start of stimulation, 2 weeks after start of stimulation, end of treatment (EOT), EOT + 1mo, EOT + 2 mo, EOT + 3 mo

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame adverse Event were collected for the time frame subject was enrolled in the study. Eligibility through EOT +3 months, an average of 4 months per participant
    Adverse Event Reporting Description
    Arm/Group Title PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day)
    Arm/Group Description The PNS (3 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (3 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (6 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period. The PNS (9 hr/day) Group will receive peripheral nerve stimulation treatment for three weeks (9 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period.
    All Cause Mortality
    PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/8 (0%) 0/7 (0%)
    Serious Adverse Events
    PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/8 (37.5%) 2/8 (25%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Fall with injury 0/8 (0%) 0 1/8 (12.5%) 1 0/7 (0%) 0
    Orthopedic surgery 0/8 (0%) 0 1/8 (12.5%) 1 0/7 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    other medical condition: Cancer 2/8 (25%) 2 0/8 (0%) 0 0/7 (0%) 0
    Psychiatric disorders
    Anxiety(psychosocial) 1/8 (12.5%) 1 0/8 (0%) 0 0/7 (0%) 0
    Other (Not Including Serious) Adverse Events
    PNS (3 hr/Day) PNS (6 hr/Day) PNS (9 hr/Day)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/8 (75%) 6/8 (75%) 7/7 (100%)
    Musculoskeletal and connective tissue disorders
    Fall with injury 1/8 (12.5%) 1 2/8 (25%) 2 1/7 (14.3%) 1
    Arm fatigue/weakness/pain 0/8 (0%) 0 0/8 (0%) 0 2/7 (28.6%) 2
    Skin and subcutaneous tissue disorders
    Skin Irritation at Bandage site 5/8 (62.5%) 5 2/8 (25%) 3 4/7 (57.1%) 4
    Skin Irritation under Sprint Pad 1/8 (12.5%) 1 1/8 (12.5%) 1 0/7 (0%) 0
    Retained Lead Fragment 1/8 (12.5%) 1 1/8 (12.5%) 1 0/7 (0%) 0
    Accidental dislodgment of Lead 2/8 (25%) 2 2/8 (25%) 3 1/7 (14.3%) 1
    Skin Irritation at electrode site 1/8 (12.5%) 1 2/8 (25%) 2 2/7 (28.6%) 2

    Limitations/Caveats

    The trial did not meet the goal of 10 participants per group. Results should be interpreted with caution.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Richard Wilson, MD
    Organization MetroHealth Medical Center
    Phone 216-778-4414
    Email rwilson@metrohealth.org
    Responsible Party:
    Richard Wilson, MD, Assistant Professor, Physical Medicine and Rehabilitation, MetroHealth Medical Center
    ClinicalTrials.gov Identifier:
    NCT02928055
    Other Study ID Numbers:
    • IRB16-00510
    • R01HD075542
    First Posted:
    Oct 7, 2016
    Last Update Posted:
    Jun 18, 2021
    Last Verified:
    Jun 1, 2021